Idiopathic pulmonary fibrosis (IPF) is a progressive and generally fatal disease that causes fibrosis of the pulmonary interstitium. While many environmental agents cause diseases clinically similar to IPF, the etiology of IPF is considered unknown by definition. Current concepts of the pathogenesis of IPF suggest that environmental agents could incite the tissue injury that results in IPF; furthermore, host characteristics could have an important role in determining the magnitude of the host response to the agent initiating injury. We propose to conduct a multicenter casecontrol study of IPF to investigate risk factors for this disease. Cases (N = 300) will be ascertained at multiple collaborating centers and controls (N = 600) will be identified by telephone screening with matching for age and gender. A telephone interview will be conducted to collect information needed to test hypotheses concerning cigarette smoking, occupational exposure, indoor exposures, other environmental factors, and host factors. The planned sample size should be adequate for detecting strong effects of rare exposures and moderate effects of more common exposures. To limit disease misclassification, two pathologists, experienced with interstitial diseases of the lung, will review histopathological material from all cases to exclude entities other than IPF and to fully characterize the cases clinically. The mortality of this large series of IPF cases will also be described. The designation of many cases of pulmonary fibrosis as "idiopathic" may only reflect our limited understanding of the factors causing IPF. The case-control study proposed in this application represents an appropriate first step for evaluating the etiology of this disorder.